We have recently observed that prostaglandin F2 alpha (PGF2 alpha) is released from the brain in circhoral pulses which appear to modulate at the time of estrogen-induced gonadotrophin release from the pituitary-hypothalamic system. This finding provides a new approach to the investigation of the role of PGs in the central nervous control of gonadotrophin secretion. Sheep, surgically prepared with jugulo-carotid loops and indwelling cannulae in the lateral ventricles, will serve as model animals. The mediating and modulating effects of steroid hormones on both gonadotrophin and PG pulses will be studied during anestrus and during the breeding season in intact and ovariectomized ewes. A number of centrally active drugs known to alter PG synthesis and to block ovulation or gonadotrophin release will be examined with particular emphasis on any changes which may occur in the pulsatile pattern of prostaglandin release. Antagonists of prostaglandin action and inhibitors of prostaglandin synthesis will be employed to help determine the mechanism of action of prostaglandin in the hypothalamo-hypophyseal system. As more information on the occurrence and role of prostaglandins emerges during the projected experiments, studies will be carried out on the biosynthesis of prostaglandins in the brain in vivo using labeled precursors to define the relationship, if any, between PG release and PG synthesis. BIBLIOGRAPHIC REFERENCES: Roberts J.S., Craig, G.M. and McCracken, J.A. (1976) "Evidence for involvement of prostaglandin F2 alpha in central alpha-adrenergic receptor activity." 4th New England Endocrinology Conference, Boston, Mass. Abstract #40. Craig, G.M., Roberts, J.S. and McCracken, J.A. (1977) "Evidence for involvement of prostaglandin F2 alpha in central alpha-adrenergic receptor activity." in press.